Single-dose pevifoscorvir sodium for people with moderate liver impairment and healthy adults

A Phase 1 Non-Randomized, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety- and Tolerability of Pevifoscorvir Sodium (ALG-000184) in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function

This study gives a single oral dose of pevifoscorvir sodium to adults with moderate liver impairment and matched healthy adults to see how liver function affects the drug's levels and short-term safety.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Aligos Therapeutics (industry)
• Locations: 1 site (Orlando, Florida)
• Trial ID: NCT07342868 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label, non-randomized hepatic impairment study enrolled 16 adults divided into two cohorts: eight with moderate hepatic impairment (Child-Pugh Class B) and eight matched healthy controls. Each participant receives a single oral dose of pevifoscorvir sodium (ALG-000184) and plasma concentrations of ALG-001075 are measured over time to determine pharmacokinetics. Safety and tolerability are monitored with vital signs, ECGs, and clinical assessments during and after dosing. Participants were matched by age, body weight, and, to the extent possible, sex, and the study was conducted at a single site in Orlando, Florida.

Who should consider this trial

Good fit: Adults 18 to 75 years old who weigh over 50 kg and either have moderate hepatic impairment (Child-Pugh Class B) or normal liver function, and who meet the study's health and contraception requirements, are eligible to participate.

Not a fit: People with severe hepatic impairment, pregnant or breastfeeding women, children, or individuals with disqualifying medical conditions are unlikely to receive direct benefit from this single-dose safety and pharmacokinetic study.

Why it matters

Potential benefit: If successful, results could guide safe dosing of pevifoscorvir in people with moderate liver impairment and inform later-stage trials for chronic hepatitis B.

How similar studies have performed: Hepatic impairment pharmacokinetic studies are a standard part of drug development and have reliably identified dose adjustments for many drugs, though pevifoscorvir itself has limited prior data in this specific setting.

Eligibility criteria

Inclusion Criteria:

1. Male and Female between 18 and 75 years old
2. BMI 17.5 to 40.0 kg/m\^2 and a total body weight \>50 kg (110 lb)
3. Female subjects must either be not of childbearing potential or if they are a woman of childbearing potential, they are only eligible if they and any non- sterile, male sexual partners agree to use highly effective contraceptive therapy
4. Female subjects must have a negative serum pregnancy test at screening

Inclusion Criteria for Subjects with Normal Hepatic Function:

1. Good general health as defined by no clinically relevant abnormalities identified by Medical History and a vital signs and 12-lead electrocardiogram (ECG) assessment
2. Subjects must fit the demographic-matching criteria including body weight, age, and to the extent possible, gender
3. Normal hepatic function with no known or suspected hepatic impairment

Inclusion Criteria for Subjects with Impaired Hepatic Function:

1. Subject satisfies the criteria for Class B of the Child-Pugh classification (Child Pugh Scores 7-9 points) within 28 days of study drug administration
2. A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, Fibroscan, computerized tomography scan, or magnetic resonance imaging (MRI)
3. Stable hepatic impairment for at least 3 months prior to screening or second screening visit to demonstrate stability
4. Stable concomitant medications for the management of an individual subject's medical history for at least 28 days prior to screening Subjects must have a 12-lead ECG and vital signs assessment that meet the protocol criteria

Exclusion Criteria for All Subjects:

1. Subjects with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation
2. Subjects with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome (e.g., hypokalemia, family history of long QT Syndrome) or history or clinical evidence at screening of significant or unstable cardiac disease etc.
3. Subjects with a history of clinically significant drug allergy
4. Subjects with a recent (within 1 year of randomization) history or current evidence of drug abuse or recreational drug use
5. Excessive use of alcohol defined as regular consumption of ≥14 units/ week for women and ≥21 units/week for men
6. Unwilling to abstain from alcohol use for 48 hours prior to start of the study through end of study follow up
7. Subjects with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection. Subjects provided they met stable treatment criteria. Subjects with HIV infection may be eligible for moderate impairment cohort provided they met stable treatment criteria.

Exclusion Criteria for Subjects with Normal Hepatic Function:

1. Estimated creatinine clearance \<60 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula\] - Unless otherwise instructed by the Study Review Committee (SRC), CKD-EPI should not be corrected for subjects of African ancestry
2. Bilirubin (total, direct) \>1.2× upper limit of normal (ULN) (unless Gilbert's is suspected)
3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \> 1.2×ULN
4. Grade ≥1 Hemoglobin

Exclusion Criteria for Subjects with Impaired Hepatic Function:

1. Subjects with advanced ascites (Grade 3)
2. Subjects with refractory encephalopathy as judged by the investigator.
3. Subjects with esophageal variceal bleeding within the past 6 months prior to screening.
4. Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.
5. Estimated creatinine clearance \<60 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula\] - Unless otherwise instructed by the SRC, CKD-EPI should not be corrected for subjects of African ancestry
6. ALT or AST level ≥5×ULN
7. Serum sodium ≤125 mmol/L
8. Platelets \<50×10\^9/L
9. Grade ≥2 Hemoglobin

Where this trial is running

Orlando, Florida

• Orlando Clinical Research Center — Orlando, Florida, United States (RECRUITING)

Study contacts

• Study coordinator: Jen Rito

Conditions: Chronic Hepaititis B Infections